| First Author | Campaner S | Year | 2005 |
| Journal | Mol Cell Biol | Volume | 25 |
| Issue | 15 | Pages | 6660-72 |
| PubMed ID | 16024801 | Mgi Jnum | J:100018 |
| Mgi Id | MGI:3586393 | Doi | 10.1128/MCB.25.15.6660-6672.2005 |
| Citation | Campaner S, et al. (2005) Sil phosphorylation in a pin1 binding domain affects the duration of the spindle checkpoint. Mol Cell Biol 25(15):6660-72 |
| abstractText | SIL is an immediate-early gene that is essential for embryonic development and is implicated in T-cell leukemia-associated translocations. We now show that the Sil protein is hyperphosphorylated during mitosis or in cells blocked at prometaphase by microtubule inhibitors. Cell cycle-dependent phosphorylation of Sil is required for its interaction with Pin1, a regulator of mitosis. Point mutation of the seven (S/T)P sites between amino acids 567 and 760 reduces mitotic phosphorylation of Sil, Pin1 binding, and spindle checkpoint duration. When a phosphorylation site mutant Sil is stably expressed, the duration of the spindle checkpoint is shortened in cells challenged with taxol or nocodazole, and the cells revert to a G2-like state. This event is associated with the downregulation of the kinase activity of the Cdc2/cyclin B1 complex and the dephosphorylation of the threonine 161 on the Cdc2 subunit. Sil downregulation by plasmid-mediated RNA interference limited the ability of cells to activate the spindle checkpoint and correlated with a reduction of Cdc2/cyclin B1 activity and phosphorylation on T161 on the Cdc2 subunit. These data suggest that a critical region of Sil is required to mediate the presentation of Cdc2 activity during spindle checkpoint arrest. |
